Impact of Morphology on Iron Oxide Nanoparticles-Induced Inflammasome Activation in Macrophages Liu Liu Rui Sha Lijiao Yang Xiaomin Zhao Yangyang Zhu Jinhao Gao Yunjiao Zhang Long-Ping Wen 10.1021/acsami.8b17474.s001 https://acs.figshare.com/articles/journal_contribution/Impact_of_Morphology_on_Iron_Oxide_Nanoparticles-Induced_Inflammasome_Activation_in_Macrophages/7373885 Inflammasomes, a critical component of the innate immune system, mediate much of the inflammatory response manifested by engineered nanomaterials. Iron oxide nanoparticles (IONPs), a type of nanoparticles that have gained widespread acceptance in preclinical and clinical settings, are known to induce inflammasome activation, but how morphology affects the inflammasome-activating property of IONPs has not been addressed. In this report, we have synthesized four morphologically distinct IONPs having the same aspect ratio and similar surface charge, thus offering an ideal system to assess the impact of morphology on nanoparticle-elicited biological effect. We show that morphology was a critical determinant for IONP-induced IL-1β release and pyroptosis, with the octapod and plate IONPs exhibiting significantly higher activity than the cube and sphere IONPs. The inflammasome-activating capacity of different IONPs correlated with their respective ability to elicit intracellular reactive oxygen species generation, lysosomal damage, and potassium efflux, three well-known mechanisms for nanoparticle-facilitated inflammasome activation. Furthermore, we demonstrate that the release of IL-1β induced by IONPs was only partly mediated by NLRP3, suggesting that inflammasomes other than NLRP3 are also involved in IONP-induced inflammasome activation. Our results may have implications for designing safer nanoparticles for in vivo applications. 2018-11-06 00:00:00 morphology IONP-induced IL -1β release Macrophages Inflammasomes Iron Oxide Nanoparticles-Induced Inflammasome Activation inflammasome-activating capacity vivo applications IL -1β nanoparticle-facilitated inflammasome activation inflammasome-activating property surface charge iron oxide nanoparticles plate IONPs intracellular reactive oxygen species generation IONP-induced inflammasome activation NLRP 3 lysosomal damage sphere IONPs potassium efflux aspect ratio inflammasome activation